I. Field of the Invention
This invention pertains generally to systems and methods for providing treatment to patients who are at risk for congestive heart failure and other conditions, and more particularly, to a system and method for treating related renal conditions through local delivery of agents to the renal system.
II. Description of Related Art
Heart failure is a leading cause of morbidity and mortality in the United States. There are more than 5 million patients with heart failure and over 500,000 newly diagnosed cases each year. The proper function of the kidney is directly related to cardiac output and blood pressure. In patients with congestive heart failure (CHF), cardiac output, blood pressure and renal function can be substantially compromised. Renal function can be further compromised during surgical intervention such as an angioplasty, coronary artery bypass, valve repair and/or replacement, and the like. Additionally, a patient undergoing less invasive analogs of these procedures can be particularly susceptible to renal damage from contrast imaging.
Conventionally, patients with pulmonary edema and symptoms related to CHF are often treated via systemic administration of diuretics and/or vasodilators in order to reduce the load on the heart, increase kidney function, and reduce edema. However, since these patients already suffer from low cardiac output and related blood pressure and renal problems, these systemically administered agents can take a long time to achieve beneficial results, if any. At the same time, systemic side effects such as hypotension, which further compromise the patients, often lead to discontinued treatment prior to having a desired therapeutic effect.
Acute renal failure (“ARF”) is the sudden and temporary loss of kidney function. As such, there is an abrupt decrease in the kidney's ability to excrete waste from the blood. The change in kidney function can be attributable to many causes. Any traumatic event, such as hemorrhage, gastrointestinal fluid loss, or renal fluid loss without proper fluid replacement may cause a patient to exhibit ARF. Patients also become prone to developing ARF after receiving anesthesia, invasive surgery, or alpha-adrenergic agonists because of related systemic or renal vasoconstriction. Additionally, systemic vasodilation caused by anaphylaxis, anti-hypertensive drugs, sepsis or a drug overdose may also cause ARF. This response is likely because the body's natural defense is to temporarily shut down non-essential organs such as the kidneys; however, in the case of chronic CHF, the reduction in blood flow to the kidneys is not just temporary. Reduced cardiac output can be caused by cardiogenic shock, pericardial tamponade, massive pulmonary embolism, or the like. Notably, reduced cardiac output creates an excess of fluid in the body, which, in turn, can exacerbate CHF. More specifically, a reduction in blood flow and blood pressure in the kidneys (i.e., due to reduced cardiac output) can result in the retention of excess fluid in the body, leading, for example, to pulmonary and systemic edema. As such, there is a strong correlation between ARF, reduced cardiac output and CHF.
Various diagnostic systems and procedures employ local delivery of dye (e.g., radiopaque “contrast” agents) or other diagnostic agents that permit the external monitoring system to gather important physiological information about the patient. Patients that undergo diagnostic imaging and/or treatment procedures are usually exposed to these contrast agents or media. For example, angiography employs a hollow, tubular catheter for locally injecting radiopaque dye into a blood vessel or chamber, including coronary arteries in the case of coronary angiography, or a ventricle in the case of cardiac ventriculography. The kidneys are the body's main blood filtering tools and can be damaged from excessive exposure to high-density radiopaque contrast dye, such as during coronary-, cardiac-, or neuro-angiography procedures. These procedures can result in a condition known as radiocontrast nephropathy (RCN), wherein an acute impairment of renal function follows exposure to radiographic contrast materials. This typically results in a rise in serum creatinine levels of more than 25% above baseline, or an absolute rise of 0.5 mg/dl, within 48-72 hours. Hence, in addition to congestive heart failure (CHF), renal damage associated with RCN is a frequently observed cause of ARF. RCN is one of the most common causes of onset renal failure and renal impairment in hospital patients.
For prolonged local administration of protective agents into the renal system long dwell times may also be desirable. This can be achieved via a retrograde femoral approach, such as that commonly used in intravascular catheterization procedures. However, an antegrade approach, for example, via the brachial or radial arteries, may be more effective under specific circumstances (i.e., where a patient is not able to lay down during long dwell times due to pulmonary edema). The antegrade approach is gaining more popularity in standard coronary and other intravascular intervention, and may be particularly beneficial over femoral delivery in such cases as mentioned above where a patient will need to be able to sit up after placement of the device. Notably, when a patient is in motion during dwell periods, conventional catheter-based devices can become dislodged. For example, dislodging of a device placed in the renal arteries can occur during arm and upper body motion if placed via a brachial approach; or during leg, waist or lower body motion (such as simply sitting up after placement) if placed via a femoral approach.
Angiographic catheters and other tubular delivery catheters can be used to locally inject therapeutic agents into specific spaces and lumens into the body of CHF patients. Examples include local delivery of thrombolytic drugs such as TPA™ agent, heparin, cumadin, or urokinase into areas of vascular injury including thrombotic stroke, acute myocardial infarction, or near thrombogenic implants. In addition, various balloon catheter systems can be used for local administration of therapeutic agents into targeted body lumens or spaces associated with blood vessels. Balloon catheter systems may include balloons with porous or perforated walls that elute drug agents into surrounding tissue including walls of blood vessels. Multiple balloon catheters employ spaced balloons that are inflated to engage a lumen or vessel wall in order to isolate the intermediate catheter region from in-flow or out-flow across the balloons. A fluid agent delivery system can be coupled to the intermediate catheter region in order to fill the region with a drug. The drug is meant to affect the isolated region between the balloons.
There are some advances in the understanding of the pathophysiologic mechanisms contributing to sodium and water retention in CHF, and patients can be treated with a variety of drugs. Natriuretic peptides are a group of naturally occurring substances that act in the body to oppose the activity of the renin-angiotensin system. There are three major natriuretic peptides: atrial natriuretic or A-type peptide (ANP), which is synthesized in the atria; brain natriuretic or B-type peptide (BNP), which is synthesized in the ventricles; and C-type natriuretic peptide (CNP), which is synthesized in the brain. ANP and BNP act mainly as cardiac hormones while CNP is mostly active in the central nervous system and in peripheral tissues, including blood vessels. The natriuretic peptides ANP and BNP are also known as cardioneurohormones, and are secreted from the heart in response to increased intracardiac volume or pressure. They are secreted from the ventricles in response to volume expansion or pressure overload, and levels of BNP have been shown to be elevated in patients with left ventricular dysfunction. More specifically, both ANP and BNP are released in response to atrial and ventricular stretch, and will cause vasorelaxation, inhibition of aldosterone secretion in the adrenal cortex, and inhibition of renin secretion in the kidney. Both ANP and BNP will cause natriuresis and a reduction in intravascular volume, effects amplified by antagonism of antidiuretic hormone (ADH). For example, the natural human peptide called human B-type natriuretic peptide (HBNP) is secreted by the heart as part of the body's normal response to heart failure. The drug Natrecor® formulation (nesiritide) (manufactured by Scios Inc.) is a recombinant form of the endogenous human peptide which is intravenously administered to patients with acutely decompensated congestive heart failure (see Natrecor® (nesiritide) for Injection, Scios Inc. and U.S. Pat. Nos. 5,114,923 and 5,674,710). The physiologic effects of CNP are different from those of ANP and BNP. CNP has a hypotensive effect, but no significant diuretic or natriuretic actions. Three natriuretic peptide receptors (NPRs) have been described that have different binding capacities for ANP, BNP, and CNP. Removal of the natriuretic peptides from the circulation is affected mainly by binding to clearance receptors and enzymatic degradation in the circulation. Increased blood levels of natriuretic peptides have been found in certain disease states, suggesting a role in the pathophysiology of those diseases, including congestive heart failure (CHF), systemic hypertension, and acute myocardial infarction. The natriuretic peptides also serve as disease markers and indicators of prognosis in various cardiovascular conditions. BNP, which is synthesized in the cardiac ventricles and correlates with LV pressure, amount of dyspnea, and the state of neurohormonal modulation, makes this peptide the first potential marker for heart failure. Measurement of plasma BNP concentration is evolving as a screening technique (e.g., Biosite Diagnostics, Inc.) for identifying patients with various cardiac abnormalities regardless of etiology and degree of LV systolic dysfunction that can potentially develop into obvious heart failure and carry a high risk of a cardiovascular event (Dr. James Hill, Natriuretic Peptides in Heart Failure, University of Florida College of Medicine (2001)).
Patients suffering from CHF would enormously benefit from safe and effective local therapies or prophylaxis of renal conditions related to CHF. Clearly, there exists a clinical need for treatment that provides for a fluid overload reduction quickly, reliably, and in the absence of undesired side effects. This is particularly critical, since the CHF patient population often presents with pulmonary edema and many other serious co-morbidities. A further need exists for a bilateral renal delivery device system and method that would allow for reliable and robust positioning of the bilateral delivery/injection assembly in vivo. Such a system would work regardless of whether the patient is motion or not.